Microglial displacement of inhibitory synapses provides neuroprotection in the adult brain

Zhihong Chen, Walid Jalabi, Weiwei Hu, Hyun-Joo Park, John T. Gale, Grahame J. Kidd, Rodica Bernatowicz, Zachary C. Gossman, Jacqueline T. Chen, Ranjan Dutta and Bruce D. Trapp ()
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Zhihong Chen: Lerner Research Institute, Cleveland Clinic
Walid Jalabi: Lerner Research Institute, Cleveland Clinic
Weiwei Hu: Lerner Research Institute, Cleveland Clinic
Hyun-Joo Park: Lerner Research Institute, Cleveland Clinic
John T. Gale: Lerner Research Institute, Cleveland Clinic
Grahame J. Kidd: Lerner Research Institute, Cleveland Clinic
Rodica Bernatowicz: Lerner Research Institute, Cleveland Clinic
Zachary C. Gossman: Lerner Research Institute, Cleveland Clinic
Jacqueline T. Chen: Lerner Research Institute, Cleveland Clinic
Ranjan Dutta: Lerner Research Institute, Cleveland Clinic
Bruce D. Trapp: Lerner Research Institute, Cleveland Clinic

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: Abstract Microglia actively survey the brain microenvironment and play essential roles in sculpting synaptic connections during brain development. While microglial functions in the adult brain are less clear, activated microglia can closely appose neuronal cell bodies and displace axosomatic presynaptic terminals. Microglia-mediated stripping of presynaptic terminals is considered neuroprotective, but the cellular and molecular mechanisms are poorly defined. Using 3D electron microscopy, we demonstrate that activated microglia displace inhibitory presynaptic terminals from cortical neurons in adult mice. Electrophysiological recordings further establish that the reduction in inhibitory GABAergic synapses increased synchronized firing of cortical neurons in γ-frequency band. Increased neuronal activity results in the calcium-mediated activation of CaM kinase IV, phosphorylation of CREB, increased expression of antiapoptotic and neurotrophic molecules and reduced apoptosis of cortical neurons following injury. These results indicate that activated microglia can protect the adult brain by migrating to inhibitory synapses and displacing them from cortical neurons.

Date: 2014
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DOI: 10.1038/ncomms5486

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